Hantavirus infection-related acute inflammatory demyelinative polyradiculoneuropathy: A case report and literature review

Rationale: Hemorrhagic fever with renal syndrome (HFRS) is a common infectious disease in China. As a complication of post-Hantavirus infection, Guillain–Barre syndrome (GBS) was rarely previously reported. Here, we described a case of acute inflammatory demyelinative polyradiculoneuropathy secondary to Hantavirus infection in spring of 2023. We also made a summary of the clinical features from previous reported cases. Patient concerns: A young male patient complained a fever with headache, who was subsequently diagnosed with HFRS with positive serum Hantavirus antibody IgM. Two weeks later, he presented sustained back pain, obvious numbness located in 4 extremities, chest and abdomen, facial dyskinesia and 4 extremities muscle weakness. Diagnosis, Interventions, and Outcomes: He was rapidly diagnosed with GBS by typical cerebrospinal fluid change and the electromyography examination presentation, which was verified associated with hantavirus infection. He was treated with intravenous immunoglobulin infusion followed by rehabilitation treatment. He got a complete recovery within 4 months after disease onset. Lessons: GBS was an uncommon manifestation of Hantavirus infection. GBS should be considered when acute limb weakness happens in cases with HFRS. A multidisciplinary team could make a rapid diagnosis and optimal treatment when nervous system disorders occurred.


Case presentation
A 34-year-old Chinese man living in a county town of Liaoning province in northeast China, complained a fever with headache The authors have no funding and conflicts of interest to disclose.
The patient has provided written informed consent for the publication of this report.Although his urine volume was normal, the ultrasound examination showed the coarse and slightly enhanced echo of bilateral kidneys parenchyma.The HFRS was considered.On April 8, 2023, his temperature was normal and peripheral blood white blood cell counts, platelet counts, and serum creatinine level returned to normal.On April 12, 2023, he complained sustained back pain, followed by obvious numbness located in 4 extremities, chest and abdomen, accompanied by facial dyskinesia and 4 extremities muscle weakness.Then he adopted a referral to our hospital in April 18, 2023.The physical examination presented dysfunction in right eyes closing, frowning, grinning, and cheek blowing.The weakened muscle power was observed in double upper limb (grade 5-/5) and double lower limb (grade 4-/5).The decreased muscle tone of 4 extremities and decreased deep tendon reflexes were also found without pathological reflex.He presented mild difficulty of urination and defecation.He had no arrhythmia and blood pressure fluctuation.He had no respiratory distress and dysphagia.Brain magnetic resonance imaging (MRI) was normal, and spinal gadolinium-enhanced MRI showed linear enhancement at the nerve root (Fig. 1).The cerebrospinal fluid (CSF) pressure was 150 mm H 2 O, protein level was 2047 mg/L, cell count was 23 × 10 6 /L, acid-fast stain and India ink stain were negative, Hantavirus antibody IgM and IgG (Diagnostic kit for antibody to Hantavirus-colloidal gold, XiaMen BOSON biotech Co. Ltd, Fujian Province,China) were positive in CSF with negative culture results of bacteria and fungus.Serum Epstein-Barr virus-IgM antibody, herpes simplex virus -IgM antibody, cytomegalovirus-IgM antibody were all negative.The antiganglioside antibodies (AGA) (Beijing Hightrust Diagnostics, Co. Ltd., China) were negative in both peripheral blood and CSF.
No pathogens had been detected by the metagenomic nextgeneration sequencing (mNGS, BGI-Shenzhen, Guangdong Province, China) using CSF sample.The electromyography examination revealed peripheral motor and sensory nerve injuries involving with demyelinating and nerve axon.The abnormal results included slowed conduction, prolonged latency and reduced amplitude of evoked velocity located in motor nerves involving with bilateral median nerve, bilateral ulnar nerve and bilateral common peroneal nerve, and slowed conduction located in sensory nerves involving with bilateral median nerve, bilateral ulnar nerve and bilateral medial plantar nerve.The slowed conduction was also observed in F waves of bilateral ulnar nerve.Hantavirus infection-associated AIDP was considered, which agreed with Brighton criteria level 1 and the criteria of National Institute of Neurological Disorder and stroke. [22,23]Then the paralysis progression was observed in his double lower limbs.The proximal muscle strength of both lower limbs was grade 2 while the distal muscle strength of both lower limbs was grade 1.After IVIG (0.4 g/kg) for 5 days, the paralysis progression stopped, followed by a vanished numbness and a slow muscle power recovery.At day 14 of admission, he adopted a structured rehabilitation program. [24,25]The physical therapy, occupational therapy, electric standing bed, low-frequency electrical stimulation and acupuncture were used.A month later, his limb function was significantly improved.On discharge (May 31, 2023), he could realize 50 m of walking distance on his own.On August 30, 2023, he could walk fluently without facial paralysis.

Discussion and conclusions
This case was characterized by mild HFRS as the first presentation and subsequent AIDP as the second presentation, who underwent a multidisciplinary treatment and got a rapidly clinical improvement.The clinical features from previous reported 6 GBS cases of Hantavirus infection were summarized in Figure 1.A case with Hantavirus infection-related chronic inflammatory demyelinating polyneuropathy was excluded. [20]n total, 4 cases came from Europe and 2 came from Asia.They presented GBS at 1 to 2 weeks after HFRS onset.The distribution of HFRS clinical types were mild (2 cases), moderate (1 case), and severe (3 cases).There were 4 male cases and 2 female cases.The ages were between 27 and 62 years old.Albuminocytologic dissociation was found in 5 cases.The MRI examination was carried out in 2 cases.Spinal images on gadolinium-enhanced MRI in our case showed linear enhancement at the nerve root, which was identical to previous report. [26]The AGA detection has not been ordinarily carried out in Hantavirus-infected cases with GBS.Nerve conduction studies can identify various subtypes, which was carried out in 5 cases.IVIG were applied to 3 patients and plasma-exchange were applied to 2 patients.There were 3 cases with respiratory distress and 2 cases required mechanical ventilation.All cases survived.A mild form of HFRS was commonly misdiagnosed at admission.According to clinical presentation, epidemiological data, and positive serological Hantavirus IgM or 4 times elevation of Hantavirus IgG using double serum samples, Hantavirus infection could be verified. [27]Furthermore, reverse transcription-polymerase chain reaction assays was also an alternative diagnosis tool. [28]Although the incidence of HFRS in China gradually decreased, which in Liaoning was still moderately endemic especially in spring and winter. [29]As a common etiology of acute flaccid paralysis, GBS is an immune-mediated disease, which usually occurs within 2 weeks postantecedent infection. [30]Although most patients recover well, GBS could present a life-threatening condition, treatment-related fluctuations/relapses and a long-term sequela.Plasma-exchange or IVIG should be early applied to treat GBS as soon as possible.

Figure 1 .
Figure 1.Gadolinium-enhanced MRI of lumbar segment of spinal cord of this case and clinical features in Hantavirus infected cases with Guillain-Barre syndrome.The arrows showed the linear enhancement at the nerve root-(A) sagitta, (B) coronal, and (C) transverse view.